tbuckley/cabot-search huggingface dataset:
A genetically engineered <i>Plasmodium falciparum</i> parasite vaccine provides protection from controlled human malaria infection
Authors: Sean C. Murphy, Ashley M. Vaughan, James G. Kublin, Matthew Fishbauger, Annette M. Seilie, Kurtis P. Cruz, Tracie Mankowski, Melike Firat, Sara Magee, Will Betz, Heather Kain, Nelly Camargo, Meseret T. Haile, Janna Armstrong, Emma Fritzen, Nina Hertoghs, Sudhir Kumar, D. Noah Sather, Leeya F. Pinder, Gregory A. Deye, Shirley Galbiati, Casey Geber, Jessica Butts, Lisa A. Jackson, Stefan H. I. Kappe
Journal: Science Translational Medicine (2022)

Genetically engineered live Plasmodium falciparum sporozoites constitute a potential platform for creating consistently attenuated, genetically defined, whole-parasite vaccines against malaria through targeted gene deletions. Such genetically attenuated parasites (GAPs) do not require attenuation by irradiation or concomitant drug treatment. We previously developed a P. falciparum (Pf) GAP with deletions in P52, P36, and SAP1 genes (PfGAP3KO) and demonstrated its safety and immunogenicity in humans. Here, we further assessed safety, tolerability, and immunogenicity of the PfGAP3KO vaccine and tested its efficacy against controlled human malaria infection (CHMI) in malaria-naïve subjects. The vaccine was delivered by three (n = 6) or five (n = 8) immunizations with ~200 PfGAP3KO-infected mosquito bites per immunization. PfGAP3KO was safe and well tolerated with no breakthrough P. falciparum blood stage infections. Vaccine-related adverse events were predominately localized urticaria related to the numerous mosquito bites administered per vaccination. CHMI via bites with mosquitoes carrying fully infectious Pf NF54 parasites was carried out 1 month after the last immunization. Half of the study participants who received either three or five PfGAP3KO immunizations remained P. falciparum blood stage negative, as shown by a lack of detection of Plasmodium 18S rRNA in the blood for 28 days after CHMI. Six protected study participants received a second CHMI 6 months later, and one remained completely protected. Thus, the PfGAP3KO vaccine was safe and immunogenic and was capable of inducing protection against sporozoite infection. These results warrant further evaluation of PfGAP3KO vaccine efficacy in dose-range finding trials with an injectable formulation.
Outcomes of a Hybrid Ophthalmology Telemedicine Model for Outpatient Eye Care During COVID-19
Authors: Nedda Sanayei, Melanie M. Albrecht, Diana C. Martin, Nicolas Marin, Shaunt Fereshetian, Steven Baker, Manju L. Subramanian, Steven Ness, Nicole H. Siegel, Xuejing Chen
Journal: JAMA Network Open (2022)

Importance The hybrid ophthalmology telemedicine model asynchronously pairs an imaging appointment by a technician with a subsequent virtual appointment by a clinician. Although it has been mentioned in several studies as an alternative to standard in-person care during the COVID-19 pandemic, outcomes of this alternative clinical care model remain to be evaluated. Objective To investigate the outcomes associated with the hybrid ophthalmology telemedicine model during the COVID-19 pandemic for nonurgent and nonprocedural ophthalmological care. Design, Setting, and Participants Retrospective, cross-sectional study of all hybrid visits scheduled during the year 2020 in a single academic, hospital-based eye clinic in Boston, Massachusetts. All hybrid ophthalmology telemedicine visits completed in the year 2020 by opthalmologists and optometrists were included. Data were analyzed from January to December 2020. Exposures Hybrid telemedicine clinical encounters. Main Outcomes and Measures Four outcome metrics were calculated: (1) need for subsequent procedure visit, (2) medication change, (3) nonurgent, and (4) urgent consultation with another eye clinician. Adverse outcomes were defined as irreversible vision loss and the need for additional in-person evaluation to reach a management decision. Results From April 9 to December 30, 2020, 889 patients (506 female patients [56.9%]; mean [SD] age, 62.1 [14.5] years; age range, 13-98 years) completed 940 hybrid visits. The most common visit indications were glaucoma (424 visits [45.1%]) and retinal diseases (499 visits [53.1%]). A total of 25 visits (2.7%) led to a procedure, 22 visits (2.3%) led to a change in medication, and 44 visits (4.7%) were referred for nonurgent consultation with another subspecialty with no instances of urgent referrals. Sixteen patients (1.7%) were referred to the on-call clinician for a same-day emergency in-person visit or recommended for a subsequent standard in-person visit to reach a management decision. There were no cases of irreversible vision loss following a hybrid visit. Conclusions and Relevance These findings suggest that with the appropriate patient selection and clinical setting, the hybrid ophthalmology telemedicine model may be a good alternative to standard in-person visits, particularly for patients with glaucoma and retinal diseases.
Intrinsic connectivity of the human brain provides scaffold for tau aggregation in clinical variants of Alzheimer’s disease
Authors: Joseph Therriault, Tharick A. Pascoal, Mélissa Savard, Sulantha Mathotaarachchi, Andréa L. Benedet, Mira Chamoun, Cécile Tissot, Firoza Z. Lussier, Nesrine Rahmouni, Jenna Stevenson, Muhammad Naveed Iqbal Qureshi, Min Su Kang, Émilie Thomas, Paolo Vitali, Jean-Paul Soucy, Gassan Massarweh, Paramita Saha-Chaudhuri, Serge Gauthier, Pedro Rosa-Neto
Journal: Science Translational Medicine (2022)

Alzheimer’s disease (AD) phenotypes might result from differences in selective vulnerability. Evidence from preclinical models suggests that tau pathology has cell-to-cell propagation properties. Therefore, here, we tested the cell-to-cell propagation framework in the amnestic, visuospatial, language, and behavioral/dysexecutive phenotypes of AD. We report that each AD phenotype is associated with a distinct network-specific pattern of tau aggregation, where tau aggregation is concentrated in brain network hubs. In all AD phenotypes, regional tau load could be predicted by connectivity patterns of the human brain. Furthermore, regions with greater connectivity displayed similar rates of longitudinal tau accumulation in an independent cohort. Connectivity-based tau deposition was not restricted to a specific vulnerable network but was rather a general property of brain organization, linking selective vulnerability and transneuronal spreading models of neurodegeneration. Together, this study indicates that intrinsic brain connectivity provides a framework for tau aggregation across diverse phenotypic manifestations of AD.
Challenging full-thickness resection of post endoscopic mucosectomy residual scar in right colon, accessed via a balloon-dilated stoma
Authors: Francesco Azzolini, Francesco Vito Mandarino, Alberto Barchi, Lorella Fanti, Edi Viale, Dario Esposito, Silvio Danese
Journal: Endoscopy (2022)

In recent years, the spectrum of endoscopic colorectal resection methods for mucosal carcinomas and scar lesions that show no lifting sign has been extended by the use of full-thickness resection (FTR) [1].
Third Asia-Pacific consensus recommendations on colorectal cancer screening and postpolypectomy surveillance
Authors: Joseph J Y Sung, Han-Mo Chiu, David Lieberman, Ernst J Kuipers, Matthew D Rutter, Finlay Macrae, Khay-Guan Yeoh, Tiing Leong Ang, Vui Heng Chong, Sneha John, Jingnan Li, Kaichun Wu, Simon S M Ng, Govind K Makharia, Murdani Abdullah, Nozomu Kobayashi, Masau Sekiguchi, Jeong-Sik Byeon, Hyun-Soo Kim, Susan Parry, Patricia Anne I Cabral-Prodigalidad, Deng-Chyang Wu, Suparkij Khomvilai, Rashid N Lui, Sunny Wong, Yu-Min Lin, E Dekker
Journal: Gut (2022)

The Asia-Pacific region has the largest number of cases of colorectal cancer (CRC) and one of the highest levels of mortality due to this condition in the world. Since the publishing of two consensus recommendations in 2008 and 2015, significant advancements have been made in our knowledge of epidemiology, pathology and the natural history of the adenoma-carcinoma progression. Based on the most updated epidemiological and clinical studies in this region, considering literature from international studies, and adopting the modified Delphi process, the Asia-Pacific Working Group on Colorectal Cancer Screening has updated and revised their recommendations on (1) screening methods and preferred strategies; (2) age for starting and terminating screening for CRC; (3) screening for individuals with a family history of CRC or advanced adenoma; (4) surveillance for those with adenomas; (5) screening and surveillance for sessile serrated lesions and (6) quality assurance of screening programmes. Thirteen countries/regions in the Asia-Pacific region were represented in this exercise. International advisors from North America and Europe were invited to participate.
Comparison of Home-Based vs Center-Based Cardiac Rehabilitation in Hospitalization, Medication Adherence, and Risk Factor Control Among Patients With Cardiovascular Disease
Authors: Chileshe Nkonde-Price, Kristi Reynolds, Michael Najem, Su-Jau Yang, Columbus Batiste, Timothy Cotter, Debora Lahti, Nancy Gin, Tadashi Funahashi
Journal: JAMA Network Open (2022)

<h3>Importance</h3> Prior studies have suggested that participation in home-based cardiac rehabilitation (HBCR) vs center-based cardiac rehabilitation (CBCR) results in similar clinical outcomes in patients with low to moderate risk; however, outcome data from demographically diverse populations and patients who are medically complex are lacking. <h3>Objective</h3> To compare hospitalizations, medication adherence, and cardiovascular risk factor control between participants in HBCR vs CBCR. <h3>Design, Setting, and Participants</h3> This retrospective cohort study was conducted among patients in Kaiser Permanente Southern California (KPSC), an integrated health care system serving approximately 4.7 million patients, who participated in CR between April 1, 2018, and April 30, 2019, and with follow-up through April 30, 2020. Data were analyzed from January 2021 to January 2022. <h3>Exposures</h3> Participation in 1 or more HBCR or CBCR sessions. <h3>Main Outcomes and Measures</h3> The primary outcome was 12-month all-cause hospitalization. Secondary outcomes included all-cause hospitalizations at 30 and 90 days; 30-day, 90-day, and 12-month cardiovascular hospitalizations; and medication adherence and cardiovascular risk factor control at 12 months. Logistic regression was used to compare hospitalization, medication adherence, and cardiovascular risk factor control, with inverse probability treatment weighting (IPTW) to adjust for demographic and clinical characteristics. <h3>Results</h3> Of 2556 patients who participated in CR (mean [SD] age, 66.7 [11.2] years; 754 [29.5%] women; 1196 participants [46.8%] with Charlson Comorbidity Index ≥4), there were 289 Asian or Pacific Islander patients (11.3%), 193 Black patients (7.6%), 611 Hispanic patients (23.9%), and 1419 White patients (55.5%). A total of 1241 participants (48.5%) received HBCR and 1315 participants (51.5%) received CBCR. After IPTW, patients who received HBCR had lower odds of hospitalization at 12 months (odds ratio [OR], 0.79; 95% CI, 0.64-0.97) but similar odds of adherence to β-blockers (OR, 1.18; 95% CI, 0.98-1.42) and statins (OR, 1.02; 95% CI, 0.84-1.25) and of control of blood pressure (OR, 0.98; 95% CI, 0.81-1.17), low-density lipoprotein cholesterol (OR, 0.98; 95% CI, 0.81-1.20), and hemoglobin A<sub>1c</sub>(OR, 0.98; 95% CI, 0.82-1.18) at 12 months compared with patients who received CBCR. <h3>Conclusions and Relevance</h3> These findings suggest that HBCR in a demographically diverse population, including patients with high risk who are medically complex, was associated with fewer hospitalizations at 12 months compared with patients who participated in CBCR. This study strengthens the evidence supporting HBCR in previously understudied patient populations.
Symptoms of Anxiety and Depression Are Independently Associated With Impaired Awareness of Hypoglycemia in Type 1 Diabetes
Authors: Beatrice A. Pieri, Gabriella A.I. Bergin-Cartwright, Anna Simpson, Julian Collins, Anna Reid, Janaka Karalliedde, Anna Brackenridge, Matthew Hotopf, Sufyan Hussain
Journal: Diabetes Care (2022)

OBJECTIVE We tested the hypothesis that impaired awareness of hypoglycemia (IAH) is independently associated with symptoms of anxiety and depression in type 1 diabetes. RESEARCH DESIGN AND METHODS In this cross-sectional observational study in 950 adults with type 1 diabetes, associations were examined using multiple regression models, adjusting for sociodemographic and clinical characteristics. RESULTS Prevalence for probable anxiety, depression, and IAH were 9.4%, 9.8%, and 22.6%, respectively. When included in separate regression models, both depression and anxiety were independently associated with an increased odds of IAH and robust to adjustment (odds ratio 3.64 [95% CI 2.19–6.04] and 2.46 [1.46–4.14], respectively). Further analysis demonstrated a dose-response relationship between increased severity of probable mental disorder and increased odds of having IAH (P &amp;lt; 0.001). CONCLUSIONS The robust independent relationship between probable anxiety and depression with IAH demonstrates the need for routine psychological assessment and management of people with type 1 diabetes and IAH.
Ublituximab versus Teriflunomide in Relapsing Multiple Sclerosis
Authors: Lawrence Steinman, Edward Fox, Hans-Peter Hartung, Enrique Alvarez, Peiqing Qian, Sibyl Wray, Derrick Robertson, DeRen Huang, Krzysztof Selmaj, Daniel Wynn, Gary Cutter, Koby Mok, Yanzhi Hsu, Yihuan Xu, Michael S. Weiss, Jenna A. Bosco, Sean A. Power, Lily Lee, Hari P. Miskin, Bruce A.C. Cree
Journal: New England Journal of Medicine (2022)

The monoclonal antibody ublituximab enhances antibody-dependent cellular cytolysis and produces B-cell depletion. Ublituximab is being evaluated for the treatment of relapsing multiple sclerosis.
Molecular heterogeneity and commonalities in pancreatic cancer precursors with gastric and intestinal phenotype
Authors: Sven-Thorsten Liffers, Laura Godfrey, Lisa Frohn, Lena Haeberle, Aslihan Yavas, Rita Vesce, Wolfgang Goering, Friederike V Opitz, Nickolas Stoecklein, Wolfram Trudo Knoefel, Anna Melissa Schlitter, Guenter Klöppel, Elisa Espinet, Andreas Trumpp, Jens T Siveke, Irene Esposito
Journal: Gut (2022)

Due to the limited number of modifiable risk factors, secondary prevention strategies based on early diagnosis represent the preferred route to improve the prognosis of pancreatic ductal adenocarcinoma (PDAC). Here, we provide a comparative morphogenetic analysis of PDAC precursors aiming at dissecting the process of carcinogenesis and tackling the heterogeneity of preinvasive lesions.
<i>Notes From the Field:</i> Coccidioidomycosis Outbreak Among Wildland Firefighters — California, 2021
Authors: Marisa A.P. Donnelly, Dorothy Maffei, Gail L. Sondermeyer Cooksey, Thomas J. Ferguson, Seema Jain, Duc Vugia, Barbara L. Materna, Amanda Kamali
Journal: MMWR Morbidity and Mortality Weekly Report (2022)

Coccidioidomycosis, also known as Valley fever, is caused by inhalation of spores of the soil-dwelling fungi Coccidioides spp.Although most illness is mild, coccidioidomycosis can cause severe disease resulting in hospitalization or death.On July 28, 2021, the California Department of Forestry and Fire Protection (CAL FIRE) notified the California Department of Public Health (CDPH) of seven wildland firefighters from two crews who had respiratory illness.Crew A (19 members) and crew B (21 members) had worked on wildfires in late June 2021 near the Tehachapi Mountains, a California region with historically high coccidioidomycosis incidence.*Among the seven symptomatic firefighters, three cases of coccidioidomycosis were laboratory-confirmed; two patients developed severe disease.All three firefighters with confirmed coccidioidomycosis reported working in dusty conditions without wearing respiratory protection.Because no vaccine for coccidioidomycosis currently exists, correct use of respiratory protection is important for preventing coccidioidomycosis, especially in regions with high disease incidence.During July 17-August 4, 2021, the seven ill firefighters each visited an emergency department two or three times with cough, chest pain, or shortness of breath; all received negative test results for SARS-CoV-2, the virus that causes COVID-19.Three of the seven firefighters were hospitalized, had serologic test results that were positive for coccidioidomycosis, and were treated with antifungal medication.CDPH interviewed these three patients and reviewed their medical records.Coccidioidomycosis serologic test results for the other four firefighters were negative; however, repeat serology is often suggested if coccidioidomycosis is suspected.† Two of these four were retested and results remained negative and were managed in ambulatory clinics, and two were lost to follow-up.All confirmed cases occurred in patients who worked on crew B, resulting in an attack rate for confirmed cases of 14.3% (three of 21).The three confirmed cases occurred in men aged 25-34 years, none of whom had any remarkable past medical history.Two patients reported Hispanic or Latino race or ethnicity, and * https://www.cdph.ca.
Gel immersion endoscopic mucosal resection for a gastric neoplasm with a background of fundic gland polyposis
Authors: Hidenori Kimura, Masayuki Oi, Yukihiro Morita, Shigeki Bamba, Osamu Inatomi, Akira Andoh
Journal: Endoscopy (2022)

Endoscopic submucosal dissection for a gastric neoplasm at the greater curvature of the upper gastric body with polyposis is challenging because of the ease of submersion in water, difficult mucosal incision due to background polyposis, and frequent bleeding during incision. Alternatively, conventional endoscopic mucosal resection (EMR) is a simple and convenient resection method. However, frequent piecemeal resection is concerning [1]. Here, we demonstrate gel immersion EMR for the aforementioned lesion.
Giant Brunner’s gland hamartoma of the duodenal bulb removed by endoscopic submucosal dissection
Authors: Miguel Pantaleón Sánchez, Mathieu Pioche, Mariana Figueiredo Ferreira, Mariana Milashka Brihay, Jérôme Rivory, Clara Yzet
Journal: Endoscopy (2022)

A duodenal Brunner's gland hamartoma is an extremely rare benign tumor of the duodenum, representing less than 1 % of primary tumors of the small intestine [1]. Most patients are asymptomatic, but sometimes the condition can cause symptoms such as obstruction or gastrointestinal hemorrhage [2]. In symptomatic patients, endoscopic or surgical treatment is required. When possible, endoscopic management is the first-line treatment, especially for pedunculated lesions [3].
Managing perforations during endoscopic resection of gastrointestinal lesions
Authors: Katie Siggens, Shahila Perveen Aslam, Hein Htet, Mohamed Abdelrahim, Pradeep Bhandari
Journal: Endoscopy (2022)

Endoscopic submucosal dissection (ESD) and endoscopic mucosal resection (EMR) carry a risk of perforation (4 %–10 % and < 1 %, respectively [1] [2]). It is essential that perforations are identified early during resection so they can be managed endoscopically to optimize patient outcomes.
Lipid nanoparticles produce chimeric antigen receptor T cells with interleukin-6 knockdown in vivo
Authors: Jing-e Zhou, Lei Sun, Yujie Jia, Zhehao Wang, Tengshuo Luo, Jingwen Tan, Xiaoyan Fang, Hongjia Zhu, Jing Wang, Lei Yu, Zhiqiang Yan
Journal: Journal of Controlled Release (2022)
Review of CDC’s Suspension of and Advance Written Approval Process for Dogs Entering the United States from Egypt — May 2019–December 2020
Authors: Michelle Latzer, Emily G. Pieracci, Ashley Altenburger, Kendra E. Stauffer, Clive M. Brown
Journal: MMWR Morbidity and Mortality Weekly Report (2022)

Dog-maintained rabies virus variant (DMRVV) was eliminated in the United States in 2007. During 2015–2019, three dogs with rabies were imported into the United States from Egypt, where DMRVV is endemic. CDC developed a risk mitigation strategy, in consultation with a diverse group of subject matter experts, that permitted 296 dogs to be imported from Egypt during May 10, 2019–December 31, 2020, minimizing the risk for future rabid dog importations. The broadly vetted risk mitigation strategy, which included serologic testing for rabies antibody titer, improved CDC’s ability to ensure that imported dogs from Egypt posed no public health risk in the United States. This strategy could be used to guide future policy decisions regarding dog importations.
Analysis of Quality-of-Life Outcomes by Drug Class in Cancer Clinical Trials—Reply
Authors: Bishal Gyawali, Elizabeth Eisenhauer, Michael Brundage
Journal: JAMA Oncology (2022)

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Mast cell–derived factor XIIIA contributes to sexual dimorphic defense against group B streptococcal infections
Authors: Adrian M. Piliponsky, Kavita Sharma, Phoenicia Quach, Alyssa Brokaw, Shayla Nguyen, Austyn Orvis, Siddhartha S. Saha, Nyssa Becker Samanas, Ravin Seepersaud, Yu Ping Tang, Emily Mackey, Gauri Bhise, Claire Gendrin, Anna Furuta, Albert J. Seo, Eric Guga, Irina Miralda, Michelle Coleman, Erin L. Sweeney, Charlotte A. Bäuml, Diana Imhof, Jessica M. Snyder, Adam J. Moeser, Lakshmi Rajagopal
Journal: Journal of Clinical Investigation (2022)

Invasive bacterial infections remain a major cause of human morbidity. Group B streptococcus (GBS) are Gram-positive bacteria that cause invasive infections in humans. Here, we show that factor XIIIA-deficient (FXIIIA-deficient) female mice exhibited significantly increased susceptibility to GBS infections. Additionally, female WT mice had increased levels of FXIIIA and were more resistant to GBS infection compared with isogenic male mice. We observed that administration of exogenous FXIIIA to male mice increased host resistance to GBS infection. Conversely, administration of a FXIIIA transglutaminase inhibitor to female mice decreased host resistance to GBS infection. Interestingly, male gonadectomized mice exhibited decreased sensitivity to GBS infection, suggesting a role for gonadal androgens in host susceptibility. FXIIIA promoted GBS entrapment within fibrin clots by crosslinking fibronectin with ScpB, a fibronectin-binding GBS surface protein. Thus, ScpB-deficient GBS exhibited decreased entrapment within fibrin clots in vitro and increased dissemination during systemic infections. Finally, using mice in which FXIIIA expression was depleted in mast cells, we observed that mast cell-derived FXIIIA contributes to host defense against GBS infection. Our studies provide insights into the effects of sexual dimorphism and mast cells on FXIIIA expression and its interactions with GBS adhesins that mediate bacterial dissemination and pathogenesis.